6-29828592-A-T

Variant names:

• chr6-29828592-A-T
• rs3873252
• NM_001384290.1:c.393A>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The ENST00000360323.11(HLA-G):​c.393A>T​(p.Gly131Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0641 in 1,612,852 control chromosomes in the GnomAD database, including 4,447 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.052 (384 hom., cov: 32)
  • Exomes 𝑓: 0.065 (4063 hom.)
• Consequence: HLA-G ENST00000360323.11 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.859
• Publications: 7 publications found

Genes affected

HLA-G (HGNC:4964): (major histocompatibility complex, class I, G) HLA-G belongs to the HLA class I heavy chain paralogues. This class I molecule is a heterodimer consisting of a heavy chain and a light chain (beta-2 microglobulin). The heavy chain is anchored in the membrane. HLA-G is expressed on fetal derived placental cells. The heavy chain is approximately 45 kDa and its gene contains 8 exons. Exon one encodes the leader peptide, exons 2 and 3 encode the alpha1 and alpha2 domain, which both bind the peptide, exon 4 encodes the alpha3 domain, exon 5 encodes the transmembrane region, and exon 6 encodes the cytoplasmic tail. [provided by RefSeq, Jul 2008]

HCG4P8 (HGNC:22927): (HLA complex group 4 pseudogene 8)

HLA-F-AS1 (HGNC:26645): (HLA-F antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP7: Synonymous conserved (PhyloP=-0.859 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.182 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000360323.11. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-G	NM_001384290.1	MANE Select	c.393A>T	p.Gly131Gly	synonymous	Exon 3 of 7	NP_001371219.1
	HLA-G	NM_001363567.2		c.408A>T	p.Gly136Gly	synonymous	Exon 4 of 8	NP_001350496.1
	HLA-G	NM_001384280.1		c.408A>T	p.Gly136Gly	synonymous	Exon 5 of 9	NP_001371209.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-G	ENST00000360323.11	TSL:6 MANE Select	c.393A>T	p.Gly131Gly	synonymous	Exon 3 of 7	ENSP00000353472.6
	HLA-G	ENST00000376828.6	TSL:6	c.408A>T	p.Gly136Gly	synonymous	Exon 4 of 8	ENSP00000366024.2
	HLA-G	ENST00000478355.5	TSL:6	n.393A>T		non_coding_transcript_exon	Exon 3 of 6

Frequencies

GnomAD3 genomes AF: 0.0523 AC: 7949 AN: 151976 Hom.: 380 Cov.: 32

Gnomad AFR AF: 0.0124

Gnomad AMI AF: 0.0976

Gnomad AMR AF: 0.0445

Gnomad ASJ AF: 0.0568

Gnomad EAS AF: 0.192

Gnomad SAS AF: 0.166

Gnomad FIN AF: 0.0393

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0609

Gnomad OTH AF: 0.0536

GnomAD2 exomes AF: 0.0737 AC: 18227 AN: 247242 AF XY: 0.0792

Gnomad AFR exome AF: 0.0112

Gnomad AMR exome AF: 0.0372

Gnomad ASJ exome AF: 0.0587

Gnomad EAS exome AF: 0.204

Gnomad FIN exome AF: 0.0388

Gnomad NFE exome AF: 0.0588

Gnomad OTH exome AF: 0.0706

GnomAD4 exome AF: 0.0653 AC: 95358 AN: 1460758 Hom.: 4063 Cov.: 55 AF XY: 0.0682 AC XY: 49596 AN XY: 726694

African (AFR) AF: 0.00938 AC: 314 AN: 33480

American (AMR) AF: 0.0387 AC: 1732 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.0592 AC: 1548 AN: 26136

East Asian (EAS) AF: 0.111 AC: 4387 AN: 39700

South Asian (SAS) AF: 0.152 AC: 13129 AN: 86256

European-Finnish (FIN) AF: 0.0398 AC: 2082 AN: 52340

Middle Eastern (MID) AF: 0.0643 AC: 371 AN: 5768

European-Non Finnish (NFE) AF: 0.0605 AC: 67303 AN: 1111976

Other (OTH) AF: 0.0744 AC: 4492 AN: 60384

GnomAD4 genome AF: 0.0523 AC: 7955 AN: 152094 Hom.: 384 Cov.: 32 AF XY: 0.0547 AC XY: 4066 AN XY: 74360

African (AFR) AF: 0.0123 AC: 512 AN: 41488

American (AMR) AF: 0.0445 AC: 680 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0568 AC: 197 AN: 3468

East Asian (EAS) AF: 0.192 AC: 989 AN: 5158

South Asian (SAS) AF: 0.167 AC: 801 AN: 4808

European-Finnish (FIN) AF: 0.0393 AC: 416 AN: 10596

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0609 AC: 4138 AN: 67968

Other (OTH) AF: 0.0563 AC: 119 AN: 2112

Alfa AF: 0.0488 Hom.: 68

Bravo AF: 0.0486

Asia WGS AF: 0.163 AC: 564 AN: 3478

EpiCase AF: 0.0626

EpiControl AF: 0.0580

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	8.3
DANN	Benign	0.29
PhyloP100		-0.86
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3873252; hg19: chr6-29796369;